This study is designed to explore the cellular mechanisms associated with the control of detrusor and neck smooth muscle components of the urinary bladder. The primary emphasis will be placed on: contractile effects, Ca2 ion metabolism and cyclic nucleotide responses on the urinary bladder neck or detrusor to autonomic (sympathetic, cholinergic) and other naturally occurring local hormones, i.e., PG, serotonin, histamine and angiotensin. The selective blocking actions of antagonist will be employed to demonstrate the specificity of these responses to the agonist described in this study. Several antagonists that affect Ca2 ion fluxes such as local anesthetics will be used to modify Ca2 ion flux. The rabbit bladder will be employed for this study since it is easily dissected and has been shown to be essentially a ganglion free smooth muscle preparation with some prior physiological and pharmacological properties already studied in our laboratory. The methods employed will measure the effects of agonists and antagonists on the inherent motility by measuring force changes on isolated preparations that have been divided into either bladder neck or detrusor muscle segments. The effects of agonists and antagonistic drugs will be studied on the Ca2 ion metabolism using uptake and efflux methods utilizing 45Ca as the marker. These studies will be performed on in vitro preparations in isolated 2.5 ml organ baths. The lanthanum technique will also be employed to determine 45Ca compartment size as well as the influence of pharmacologic substances on this compartment size. The effects of these agents will be correlated with changes in the levels of cyclic nucleotides using immunochemical assay techniques capable of measuring cAMP and cGMP at levels of down to 5 femtomoles (10 to the minus 15th power moles). Provisions are made in the grant proposal for supplemental funding for the principal investigator for a sabbatical leave to Dr. Jean Marshall's laboratory at Brown University. During this leave period the principal investigator will be actively engaged in related work on smooth muscle on the synthesis and effects of prostaglandins as they relate to normal motility and electrical activity in visceral smooth muscle.